Exeter Chiefs backs Jack Nowell and Josh Tatupu are set for lengthy lay-offs after suffering injuries in the Amlin Cup win over Cavalieri Prato.
Samoa international Tatupu, 25, suffered a broken leg while young full-back Jack Nowell was stretchered off with a knee injury.
"With no further complications we'll expect to see Josh back before the end of the season," said boss Rob Baxter.
But Nowell could be out until the summer with his knee injury.
The England Under-18's full-back, who is dual-registered with Championship club Plymouth Albion, has suffered from knee problems for much of the season.
"He's got a bit of a troublesome knee already that we've been working pretty hard with," Baxter told BBC South West.
"It's an injury to the same area and I think with that injury now it's about Jack getting the knee 100% right rather than him pushing on.
"It doesn't require an operation, it just requires a long time rehabbing with some real quality. I think what we'll do with Jack is address every situation with his knee, and get them all sorted."
The problems mean there are fewer options for Baxter in the backs, with Fijian centre Sireli Naqelevuki also taking longer to recover than first expected from a broken arm.
The 31-year-old, who scored tries in the Chiefs opening two matches of the season, has not taken to the field since suffering the injury against Gloucester in November.
Naqelevuki was initially expected to miss just a month with the injury, but Baxter explained: "Sireli's taking slightly longer. It was a relatively severe injury, it needed a plate putting in and there's also damage to his wrist and it's taking a little bit longer to settle down than we would have liked.
"We're hopeful to get him back before the end of the season but as it is, it's an injury we have to make sure is 100% right before we progress to the next stage of his rehab."